**Investigating the network consequences of focal brain lesions through comparisons of real and simulated lesions** Tao, Y., Rapp, B., 2021. Investigating the network consequences of focal brain lesions through comparisons of real and simulated lesions. Sci. Rep. 11. https://doi.org/10.1038/s41598-021-81107-9 **Abstract** Given the increased interest in the functional human connectome, a number of computer simulation studies have sought to develop a better quantitative understanding of the effects of focal lesions on the brain’s functional network organization. However, there has been little work evaluating the predictions of this simulation work vis a vis real lesioned connectomes. One of the few relevant studies reported findings from real chronic focal lesions that only partially confirmed simulation predictions. We hypothesize that these discrepancies arose because although the effects of focal lesions likely consist of two components: short-term node subtraction and long-term network re-organization, previous simulation studies have primarily modeled only the short-term consequences of the subtraction of lesioned nodes and their connections. To evaluate this hypothesis, we compared network properties (modularity, participation coefficient, within-module degree) between real functional connectomes obtained from chronic stroke participants and “pseudo-lesioned” functional connectomes generated by subtracting the same sets of lesioned nodes/connections from healthy control connectomes. We found that, as we hypothesized, the network properties of real-lesioned connectomes in chronic stroke differed from those of the pseudo-lesioned connectomes which instantiated only the short-term consequences of node subtraction. Reflecting the long-term consequences of focal lesions, we found re-organization of the neurotopography of global and local hubs in the real but not the pseudo-lesioned connectomes. We conclude that the long-term network re-organization that occurs in response to focal lesions involves changes in functional connectivity within the remaining intact neural tissue that go well beyond the short-term consequences of node subtraction.